The objective of the proposed research is the development of a short term in vivo assay for carcinogens generally, using intact liver as the activator as well as the indicator and an early step in cancer development as the biological end-point. It is proposed to use an assay procedure for initiated hepatocytes developed in this laboratory to measure the induction of putative initiated liver parenchymal cells by many different carcinogens. The initiation will be achieved by either a single or multiple exposure of rats to a test compound at an appropriate time after the stimulation of liver cell proliferation. Following a recovery period of 2 weeks, the animals will be assayed for the pressure of initiated resistant cells by the creation of an appropriate selection environment consisting of a stimulus for cell proliferation coupled with an inhibition of the proliferation of the uninitiated majority of hepatocytes. The appearance of foci of the proliferating altered cells, measured as gamma-glutamyl-transpeptidase - positive groups of hepatocytes will be quantitated. Optimum conditions for maximum initiation and for rapid and reliable selection are to be developed.